KR102380935B1 - System and method for searching genomic regions - Google Patents

Abstract

The present invention relates to a genome region search system. The genome region search system, which searches for a reference region having a section overlapping with a specific region to be searched among reference regions having various segment lengths (M) represented by a start position and an end position and composed of sequence data, comprises: a length compensating part correcting the reference area with a combination of comparison target areas having a preset adjustment length (L); an area arranging part arranging the comparison target regions in ascending order based on a start position of the comparison target region, wherein a section length of the comparison target region is expressed by a start position and an end position; a binary search part specifying a comparison target region overlapping a section of the specific region among the comparison target regions by using a binary search method; and a reference region search part comparing the specific region with a reference region aligned in front of the comparison target region specified by the binary search method, and searching for a reference region whose section overlaps by comparing with a reference region aligned behind the comparison target region specified by the binary search method.

Description

SYSTEM AND METHOD FOR SEARCHING GENOMIC REGIONS

The present invention relates to a genome region search system and method, and more particularly, to a search system and method for quickly and accurately searching a genome region using binary search.

With the recent development of next-generation sequencing (NGS), it has become possible to analyze the entire genome of living organisms, including humans, at a high speed and at low cost.

However, it is very important for genetic engineering to efficiently process the vast amount of genomic data obtained as a result of whole genome sequencing. used

For example, when trying to find out which gene a mutation found in a patient was found, or to find out which gene the reads from sequencing data were found in, it is necessary to search while comparing genomic data.

In order to search for the results of genomic sequencing as described above, it is necessary to search while comparing genomic regions indicating a specific section on a nucleotide sequence in a specific chromosome.

However, two problems arise when comparing genome regions with each other. The first is that the search time becomes longer due to the vast amount of genome data. The second problem is that since the interval lengths of the dielectric regions are not constant and are different, even if the binary search is performed, all data with overlapping interval lengths cannot be found, resulting in lower accuracy.

As a conventional tool for searching the results of genome sequencing as described above, there is a binary interval search (layer et al., 2013) method.

This increases the speed of binary search and takes the method of finding out the interval length of two results for an accurate search, but loses the speed advantage of binary search at the point of obtaining the interval length, and the same interval When there are several regions having a start position and a section end position, there is a problem that incorrect position information may be returned instead of information including all of them.

An object of the present invention is to provide a genome region search system and method capable of accurately and quickly searching for a genome region having a plurality of intervals that are not constant.

In order to solve this problem, the genome region search system according to an embodiment of the present invention is composed of sequence data and a specific region and section to be searched among reference regions having various section lengths (M) expressed by start and end positions In the dielectric region search system for searching overlapping reference regions, the reference region comprising: a length correction unit for correcting the reference region with a combination of comparison regions having a preset adjustment length (L); a region arranging unit in which a section length of the comparison target region is expressed by a start position and an end position, and sorts the comparison target region in ascending order based on the start position of the comparison target region; a binary search unit for specifying a comparison target area in which the specific area and a section overlap among the comparison target areas using a binary search method; and comparing the specific region with the reference region aligned in front of the comparison target region specified by the binary search method, and comparing the reference region overlapping the reference region aligned behind the comparison target region specified by the binary search method and a reference area search unit for searching the area.

The length correction unit may correct the reference region into n comparison target regions satisfying Equation 1 below.

[Equation 1]

이고, 상기 비교대상영역의 끝위치는

일 수 있다.(Where S is the start position of the reference region, E is the end position of the reference region, L is the adjustment length, and n is a constant)
The starting position of the comparison target area is

and the end position of the comparison target area is

can be

를 만족하는 정수이다)(Where S is the starting position of the reference area, L is the adjustment length, and k is the

is an integer that satisfies

delete

The length correction unit may match the reference region and the corrected comparison target region with each other.

The reference region search unit may determine whether a section of the reference region matched with the comparison target region specified by the binary search method overlaps with a section of the specific region.

The binary search unit compares the N/2-th comparison target area with the specific area, and when the start position of the N/2-th comparison target area is greater than the end position of the specific area, the first to N/2-1th comparison areas The search is continued on the comparison target area, and when the start position of the specific area is larger than the end position of the N/2th comparison area, the search is performed on the N/2+1th comparison target area. Continuing, when the section between the specific region and the comparison target region overlaps, the search ends and the corresponding comparison target region can be specified.

The reference region search unit searches until a section between the comparison target region and the specific region arranged in front of the specified comparison target region does not overlap, and the comparison target region aligned behind the specified comparison target region and the specific region You can search until the sections of the region do not overlap.

In addition to the technical problems of the present invention mentioned above, other features and advantages of the present invention will be described below, or will be clearly understood by those of ordinary skill in the art from such description and description.

According to the present invention as described above, there are the following effects.

According to the present invention, not only can a large amount of area information be quickly searched by using the binary search method, but also search speed and accuracy can be achieved without missing areas by correcting the section length for area information having various section lengths. can improve

In addition, other features and advantages of the present invention may be newly recognized through embodiments of the present invention.

1 is a block diagram illustrating a schematic configuration of a dielectric region search system according to an embodiment of the present invention.
2 is a diagram for explaining a reference region made of sequence data according to an embodiment of the present invention.
3 is a view for explaining a length correction unit according to an embodiment of the present invention.
4 is a view for explaining an area alignment unit according to an embodiment of the present invention.
5 is a diagram for explaining a binary search unit according to an embodiment of the present invention.
6 is a diagram for explaining a reference region search unit according to an embodiment of the present invention.
7 is a view for comparing a comparative example according to the prior art and an embodiment according to the present invention.
8 to 11 are diagrams illustrating that the genome region search system according to an embodiment of the present invention finds a region where a section overlaps with a specific region of chromosome 1.
12 is a view for comparing the effects of Comparative Examples according to the prior art and the Example according to the present invention.

The meaning of the terms described in this specification should be understood as follows.

The singular expression is to be understood as including the plural expression unless the context clearly defines otherwise, and the terms "first", "second", etc. are used to distinguish one element from another, The scope of rights should not be limited by these terms.

It should be understood that terms such as “comprise” or “have” do not preclude the possibility of addition or existence of one or more other features or numbers, steps, operations, components, parts, or combinations thereof.

Hereinafter, preferred embodiments of the present invention designed to solve the above problems will be described in detail with reference to the accompanying drawings.

1 is a block diagram showing a schematic configuration of a genomic region search system according to an embodiment of the present invention, and FIG. 2 is a diagram for explaining a reference region composed of sequence data according to an embodiment of the present invention; 3 is a view for explaining a length correction unit according to an embodiment of the present invention, Figure 4 is a view for explaining an area aligning unit according to an embodiment of the present invention, Figure 5 is a view for explaining an embodiment of the present invention A diagram for explaining a binary search unit according to the present invention, and FIG. 6 is a view for explaining a reference region search unit according to an embodiment of the present invention.

1 to 6 , the genome region search system 1000 according to an embodiment of the present invention includes a length correction unit 100 , a region alignment unit 300 , a binary search unit 500 , and a reference region search unit. 700 , and a database DB 900 .

The genome region search system 1000 according to an embodiment of the present invention consists of sequence data (G) and a reference region (10) having various section lengths (M) expressed by a start position (S) and an end position (E). ), the reference area 10 overlapping the specific area 30 to be searched can be searched for.

Sequence data means data having certain sequence information, and the sequence data (G) shown in FIG. 2 is chromosome sequence data indicating the nucleotide sequence information of the chromosome, but is not limited thereto. All data having certain sequence information may be included. As an example, protein sequence data indicating amino acid characteristic information according to the sequence of protein residues may also be applied.

The specific region 30 used herein is sequence data to be searched, and the reference region 10 may be stored in the database 90 as known or known sequence data.

The reference region 10 and the specific region 30 can be expressed as a start position and an end position, and have a section length.

For example, in FIG. 2 , the first reference region 10a is composed of chromosomal nucleotide sequences A, T, and G, and has a starting position of 1 and an ending position of 3. That is, the position of the first reference region 10a is (1, 3), and the section length is 3. Since the second reference region 10b is composed of the chromosomal sequences G, T, T, C, and G, and the start position is 4 and the end position is 8, the position of the second reference region 10b is (4, 8) and The length of the section is 5. Since the third reference region 10c is composed of chromosomal sequences A, G, A, and C, and the start position is 9 and the end position is 12, the position of the third reference region 10c is (9, 12) and the section length is is 4

The length correction unit 100 may correct the reference region 10 having various section lengths M by a combination of the comparison target region 15 having a preset adjustment length L.

Here, each comparison target area 15 has a respective start position and an end position, but the section length L is all the same. In this case, the section length L may be arbitrarily selected.

The length correction unit 100 may correct each reference region 10 having a different section length into n comparison target regions satisfying Equation 1 below.

[Equation 1]

Here, S is the start position of the reference region, E is the end position of the reference region, L is the adjustment length, and n is a constant.
In this case, the coordinates of the comparison area used to correct the reference area are (S+(k-1)*L, S+k*L-1), and k is an integer satisfying 1≤k≤n. Here, since the number of comparison areas used to correct the reference area is n, the reference area is (S, S+L-1), ¨˙ , (S+(k-1)*L, S+n*L -1) It can consist of a combination of each comparison target area.

delete

를 만족하는 n=2이다.For example, the position of the second reference region 10b is (4, 8) and the length of the section is 5. When the adjustment length (L) is set to 3, 4

n = 2 satisfying .

The second reference region 10b includes two comparison target regions, and the positions of each comparison target region are (4, 6) and (7, 9).

The length correction unit 200 may match the reference region and the corrected comparison target region with each other and store respective start position and end position information in the database 900 .

The region aligning unit 300 may sort each comparison target region in an ascending order based on the start position of the comparison target region 15 .

Referring to FIG. 4 , the comparison target area 15 may also be arranged in ascending order based on each start position and may be displayed in Arabic numeral order, and in this case, in order to match the reference area and the corrected comparison target area In front of the Arabic numerals in the area 15 , the alphabet of the matched reference area may be attached and displayed.

For example, each comparison target area used to correct the h-th reference area (h) may be expressed as h9, h11, in which case the sort order and each position of each reference area and comparison area are stored in the database ( 900) can be stored.

The binary search unit 500 may specify a region where the specific region 30 and the section overlap among the comparison target regions 30 by a binary search method.

The binary search method selects a comparison target region located in the middle of the sequence as a random value when searching for a section overlapping a specific region in the comparison target region sorted in ascending order, so that the comparison target region located in the middle of the sequence and the specific region It is a method of comparing each other while reducing the sections until there is an overlapping section.

At this time, if there is no section where the N/2th comparison target area located in the first selected middle overlaps with the specific area, and the start position of the specific area is greater than the end position of the N/2th comparison target area, the N/2+1th comparison target area Binary search is continued for the Nth comparison target area from the area, and if the start position of the N/2th comparison area is larger than the end position of the specific area, the N/2-1th comparison area from the 1st comparison area You can continue the binary search for .

At this time, if N/2 is not a constant, you can proceed by selecting rounding or rounding down.

Referring to FIG. 5 , it can be seen that there is no overlapping section when the sixth comparison target region e6, which is in the middle of the sequence, is compared with the specific region 30 among the 12 comparison target regions 15 . At this time, since the start position of the sixth comparison target region e6 is larger than the end position of the specific region 30, the search continues with the first to fifth comparison target regions again. When the third comparison target region b3 and the specific region 30 are compared, it can be seen that there is no overlapping section. At this time, since the start position of the specific region 30 is larger than the end position of the third comparison region b3, the search continues for the fourth to fifth comparison regions. When the fourth comparison target region c4 is compared with the specific region 30, since there is an overlapping section, the binary search can be stopped and the fourth comparison target region c4 can be specified.

The reference region search unit 700 compares the reference region matched with the comparison target region specified by the binary search method with the specific region to determine whether the sections overlap. Also, the reference region search unit 700 compares the specific region with the reference region aligned in front of the comparison target region specified by the binary search method, and the reference aligned behind the comparison target region specified by the binary search method A reference region with overlapping sections can be searched for by comparison with the region.

The reference region search unit 700 searches until the section between the comparison target region and the specific region arranged in front of the specified comparison target region does not overlap, and the comparison target region and the specified comparison target region are aligned behind the specified comparison target region You can search until the sections of a specific area do not overlap.

Referring to FIG. 6 , the reference region search unit 700 may search for a reference region c that matches the specified comparison target region c4 . In addition, the comparison target area b3, the comparison target area b2, and the comparison target area a1 arranged in front of the specified comparison target area c4 may be sequentially compared with the specific area 30 . First, if the comparison target region b3 and the specific region 30 are compared, since the sections do not overlap each other, the search for the reference region aligned in front of the specified comparison target region c4 can be stopped.

In addition, the comparison target regions arranged behind the specified comparison target region c4 may be sequentially compared with the specific region 30 . First, if the comparison target region d5 and the specific region 30 are compared, the sections overlap each other, so that the reference region d can be searched and summoned. Thereafter, the comparison target region e6 and the specific region 30 are compared, and since the sections do not overlap each other, the search for the comparison target region arranged at the back can be stopped.

As described above, the genome region search system 1000 according to an embodiment of the present invention can not only quickly search for desired region information by using the binary search method, but also correct the section length of the region for region information having various section lengths. By doing so, you can search without missing areas, improving search speed and accuracy.

For example, the genomic region search system according to an embodiment of the present invention can quickly search for a specific mutation found in a patient in which gene region among numerous genes without omission.

7 is a view for comparing a comparative example according to the prior art and an embodiment according to the present invention.

Referring to FIG. 7 , in the comparative example, when the reference region 10 overlapping the x specific region 30 is searched using the binary search method, the e reference region 10 and the x specific region 30 are first compared. And since there is no overlapping section, the g reference region 10 and the x specific region 30 are compared again, and since the sections overlap, the g reference region 10 is finally searched and summoned. In this comparative example, the x-specific region 30 and the c reference region 10 overlapping the section may be omitted, resulting in poor accuracy.

On the other hand, in the embodiment, after specifying the e7 comparison target region where the section overlaps with the x specific region 30 by the binary search method, the section between the e reference region and the x specific region 30 matched with the e7 comparison target region overlaps with each other. , and sequentially comparing the reference regions and the x specific region 30 aligned in front and behind the e7 comparison target region with each other until there is a non-overlapping region.

As described above, in the embodiment, the c reference region, f reference region, g reference region, and i reference region overlapping the section x specific region 30 can be searched and recalled without omission.

8 to 11 are diagrams illustrating that the genome region search system according to an embodiment of the present invention finds a region where a section overlaps with a specific region of chromosome 1.

Referring to FIG. 8 , the length correction unit may correct a comparison target region having a preset adjustment length for a total of five reference regions for chromosome No. 1 .

The reference area is (10001, 13000), (10035, 10273), (11501, 12300), (10406, 12589), (12601, 12900) 5 areas having (existing start position, existing end position), The set adjustment length is 1000.

The reference region having the position (10001, 13000) may be combined into three comparison target regions corrected by (10001, 11000), (11001, 12000), and (12001, 13000).

Reference regions having positions (10035, 10273) may be combined into one comparison target region corrected by (10035, 11034).

Reference regions having positions (11501, 12300) may be combined into one comparison target region corrected by (11501, 12501).

The reference region having the position (10406, 12589) can be combined into three comparison target regions corrected by (10406, 11405), (11406, 12405), and (12406, 13405).

Reference regions having positions (12601, 12900) can be combined into one comparison target region corrected by (12601, 13600).

Referring to FIG. 9 , the region aligning unit may sort regions in an ascending order based on the start position of the comparison target region.

Referring to FIG. 10 , the binary search unit may specify a comparison target area of ( 12600 , 12800 ) that overlaps with a specific area of ( 12600 , 12800 ) to be searched among the sorted comparison target areas.

Next, referring to FIG. 11 , the reference region search unit compares the matched reference region, the front-aligned reference region, and the rear-aligned reference region with the specific region based on the specified comparison region of (12001, 13000). Thus, it is possible to search for a reference region where the sections overlap.

At this time, the reference region search unit can check until the specific region of (12600, 12800) and the comparison target region do not overlap, and is displayed in gray.

Among the gray areas, a reference area overlapping a specific area of (12600, 12800) and a section can be searched.

12 is a view for comparing the effects of Comparative Examples according to the prior art and the Example according to the present invention.

12, it is a chart comparing the speed and accuracy of the Example according to the present invention and Comparative Examples according to the prior art, in a total of 25 kinds of chromosomes (chromosomes 1 to 22, X, Y, MT chromosomes) 10000 areas were randomly created for each area, and the size of each area was also arbitrarily designated from 1 to 1000.

As a result, a total of 25*10000=250000 pieces of area information were created and this was defined as a reference area.

250000 specific areas to be searched were created in the same way, and an overlapping area between the specific area and the reference area was searched.

Comparative Example 1 is a binary interval search (Layer et al., 2013) method, and it proceeds by finding out the interval between a specific region and a reference region while using the binary search method.

Comparative Example 2 is a 'binning' method used by BEDtools (Aaron and Ira, 2010), which divides the entire genome into sections of a predetermined length, assigns each region to a corresponding section, and divides the divided regions into the same section. way to compare.

Looking at the execution time and accuracy of Example, Comparative Example 1, and Comparative Example 2, it can be seen that the Example is superior in speed and accuracy compared to the Comparative Examples.

The present invention described above is not limited to the above-described embodiments and the accompanying drawings, and it is in the technical field to which the present invention pertains that various substitutions, modifications and changes are possible without departing from the technical spirit of the present invention. It will be clear to those of ordinary skill in the art.

10: Reference area 15: Comparison target area
30: specific area 100: length correction unit
300: region alignment unit 500: binary search unit
700: reference region search unit 900: database
1000: genome region search system

Claims (7)

In a genomic region search system that searches for a reference region that overlaps with a specific region to be searched among reference regions consisting of sequence data and having various section lengths (M) expressed by start and end positions,
a length correction unit for correcting the reference region with a combination of comparison regions having a preset adjustment length (L);
a region arranging unit in which a section length of the comparison target region is expressed by a start position and an end position, and sorts the comparison target region in ascending order based on the start position of the comparison target region;
a binary search unit for specifying a comparison target area in which the specific area and a section overlap among the comparison target areas using a binary search method; and
A reference region in which the section overlaps by comparing the specific region with the reference region aligned in front of the comparison target region specified by the binary search method, and compared with the reference region aligned behind the comparison target region specified by the binary search method A genome region search system comprising a reference region search unit to search for According to claim 1,
The length correction unit is a dielectric region search system for correcting the reference region to n comparison target regions satisfying Equation 1 below.
[Equation 1]

(Where S is the start position of the reference region, E is the end position of the reference region, L is the adjustment length, and n is a constant) 3. The method of claim 2,
The starting position of the comparison target area is

and the end position of the comparison target area is

Human Genome Region Search System.
(Where S is the starting position of the reference area, L is the adjustment length, and k is the

is an integer that satisfies According to claim 1,
The length correction unit is a dielectric region search system for matching the reference region and the corrected comparison target region with each other. 5. The method of claim 4,
The reference region search unit is a genome region search system that checks whether a section of the reference region matched with the comparison target region specified by the binary search method overlaps with a section of the specific region. According to claim 1, wherein the binary search unit
By comparing the N/2th comparison target area with the specific area,
If the start position of the N/2-th comparison target region is larger than the end position of the specific region, the search continues for the 1st to N/2-1-th comparison target regions,
If the start position of the specific region is larger than the end position of the N/2-th comparison region, the search continues for the N/2+1-th to the N-th region to be compared,
When the section between the specific region and the comparison target region overlaps, the search is terminated and the corresponding comparison target region is specified. The method of claim 1, wherein the reference region search unit
Search until the section of the comparison target area aligned in front of the specified comparison target area does not overlap with the section of the specific area,
A genome region retrieval system that searches until a section between the comparison target region and the specific region aligned behind the specified comparison target region does not overlap.

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